C L Haggerty, 1 P A Totten, 2 S G Astete, 2 S Lee, 1 S L Hoferka, 1 S F Kelsey, 1 R B Ness 1. Clinical

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1 1 University of Pittsburgh, Pittsburgh, USA; 2 Department of Mediine, Division of Infetious Diseases, University of Washington, Seattle, USA Correspondene to: Catherine L Haggerty, University of Pittsburgh, Department of Epidemiology, 130 DeSoto Street, 516B Parran Hall, Pittsburgh, PA 15261; haggerty@pitt.edu Aepted 9 April 2008 Published Online First 29 April 2008 This paper is freely available online under the BMJ Journals unloked sheme, see sti.bmj.om/info/unloked.dtl Failure of efoxitin and doxyyline to eradiate endometrial Myoplasma genitalium and the onsequene for linial ure of pelvi inflammatory disease C L Haggerty, 1 P A Totten, 2 S G Astete, 2 S Lee, 1 S L Hoferka, 1 S F Kelsey, 1 R B Ness 1 ABSTRACT Objetives: As Myoplasma genitalium is assoiated with pelvi inflammatory disease (PID), we examined the effiay of a ommonly used PID antimirobial in treating M genitalium upper genital trat infetion. Methods: In the PID Evaluation and Clinial Health study of inpatient versus outpatient treatment, 682 women treated with efoxitin and doxyyline for linially suspeted PID had stored ervial and endometrial speimens available for analysis. In the urrent sub study, we ompared baseline endometritis, short term treatment failure (ontinued endometritis and pelvi pain 30 days following treatment) and sequelae among women with and without M genitalium, identified using PCR. Results: Endometrial M genitalium was assoiated with baseline endometritis (adjusted OR 3.0, 95% CI 1.5 to 6.1). Among women with a positive baseline M genitalium test, 41% tested positive again 30 days following treatment. Women testing positive ompared to those testing negative for M genitalium at baseline had an inreased risk of short-term treatment failure (RR 4.6, 95% CI 1.1 to 20.1). Rates of sequelae, inluding infertility (22%), reurrent PID (31%) and hroni pelvi pain (42%), were high among women testing positive for endometrial M genitalium at baseline. There was a non-signifiant trend towards inreased infertility, hroni pelvi pain and reurrent PID, and dereased pregnany and live birth following M genitalium infetion. Conlusions: M genitalium is assoiated with endometritis and short-term PID treatment failure. Cefoxitin and doxyyline, a Centers for Disease Control and Prevention reommended PID treatment regimen, is ineffetive for the treatment of M genitalium upper genital trat infetion. Myoplasma genitalium was first identified in the early 1980s among men with non-gonooal urethritis. 1 Beause this pathogen is extremely diffiult to ulture, only with polymerase hain reation (PCR) tehnology has researh into M genitalium pathogeniity progressed. Numerous studies have onfirmed the role of M genitalium in drug resistant non-gonooal urethritis, 2 3 and some have also linked M genitalium with erviitis 4 5 independent of Chlamydia trahomatis and Neisseria gonorrhoeae. Cerviitis is onsidered a risk fator for progression to pelvi inflammatory disease (PID) the ommon infetion and inflammation of the female upper genital trat, whih may lead to major reprodutive morbidity inluding infertility. 6 Although PID has polymirobial aetiology, with C trahomatis and/or N gonorrhoeae aounting for approximately a third to a half of ases, 7 8 up to 70% of PID ases have an unidentified aetiology. Baterial vaginosis-assoiated organisms have been assoiated with PID, 9 10 and beause M genitalium is assoiated with erviitis 4 5 it is reasonable to hypothesise that it also auses PID. Indeed, this organism indues salpingitis in monkeys, 11 auses morphologial hanges in iliated fallopian tube ells 12 and has been deteted in fallopian tube tissue in a woman with salpingitis. 13 Whereas studies have assoiated M genitalium with PID and endometritis, the effiay of ommonly used PID antimirobials in treating M genitalium upper genital trat infetion is unknown. MATERIALS AND METHODS Patient population Women who partiipated in the PID Evaluation and Clinial Health (PEACH) Study and had previously olleted and stored ervial and endometrial speimens were studied. The PEACH Study methods have been desribed in detail elsewhere. 7 Briefly, women aged 14 to 37 years were reruited between Marh 1996 and February 1999 from emergeny departments, obstetris and gynaeology linis, sexually transmitted disease (STD) linis and private praties at 13 US linial sites. Altogether, 831 women with linially suspeted PID, defined by pelvi pain of less than 30 days duration, pelvi organ tenderness and leukorrhea, muopurulent erviitis or untreated erviitis were enrolled. For this subsequent M genitalium study, stored endometrial and ervial speimens were available for 611 and 682 of partiipants, respetively. Randomisation and treatment Patients in the parent PEACH study were randomised to inpatient or outpatient antibioti treatment. The inpatient regimen onsisted of efoxitin (2 g) parenterally every 6 hours and doxyyline (100 mg) orally twie a day for a total of 14 days. The outpatient regimen onsisted of a single dose of efoxitin (2 g) intramusularly plus probeneid (1 g) orally, then doxyyline (100 mg) to be taken orally twie a day for 14 days. As treatment modality was not assoiated with reprodutive morbidities in the PEACH study, 7 we do not distinguish between inpatient and outpatient regimens or inlude them as a ovariate in these analyses. 338 Sex Transm Infet 2008;84: doi: /sti

2 M genitalium PCR Previously olleted ervial and endometrial speimens stored at 270uC were tested for M genitalium using the MgPa-IMW PCR assay targeting the MgPa gene 17 by tehniians masked to endometrial histology, treatment failure and reprodutive sequelae. This assay has an analytial sensitivity of 15 genomes 17 and a high linial sensitivity and speifiity relative to transription-mediated amplifiation (TMA) another M genitalium NAAT assay. 18 For all samples testing positive, a seond MgPa PCR assay was performed using another aliquot of the sample to rule out PCR produt ontamination or rossontamination; all samples initially positive were verified as positive in this onfirmatory test. Endometrial biopsies and mirobiologial studies At baseline and 30 days in the parent PEACH study, an endometrial biopsy was obtained for histology, hlamydial PCR (Rohe Diagnostis, USA), and gonooal ulture. In a subset of 352 women (240 women in the urrent sub study), endometrial speimens were ultured for Myoplasma hominis and Ureaplasma urealytium. 19 Endometrial histology was determined based on haematoxylin and eosin stained and methyl green pyronine stained biopsy tissue speimens, read separately by two referene pathologists who reviewed the slide together to reah onsensus upon disagreement. A modifiation 20 of the riteria proposed by Kiviat et al 8 was used to define endometritis. A lassifiation of endometritis was given upon finding at least five neutrophils in the endometrial surfae epithelium in the absene of menstrual endometrium and/or at least two plasma ells in the endometrial stroma. Cervial swabs were used for N gonorrhoeae ultures and C trahomatis PCR assays. Vaginal smears were Gram stained for baterial vaginosis as desribed by Nugent et al. 10 Follow up Partiipants were monitored with in-person visits at 5 and 30 days. Subsequent telephone interviews were onduted every 3 months during the first year and then every 4 months until June 2004, at whih point we had follow up information for 541 women, representing a mean follow up of 84 months. Reprodutive outomes inluded the ourrene of a first pregnany, first live birth, infertility, hroni pelvi pain and reurrent PID. Infertility was defined when a sexually ative woman with at least 12 months of follow up did not report oneption (positive urine or blood test or dotor s diagnosis of pregnany) despite rare or no use of a ontraeptive method. Chroni pelvi pain was defined as pain reported during at least two onseutive follow up interviews; thereby, suggesting a minimum of 6 months duration. Reurrent PID was self reported and verified whenever medial reords were available (in 45% of the ohort). Reurrent PID was onfirmed in 76% of medial reords and rates by self report and medial reord review were similar. 7 As few women experiened an etopi pregnany during follow up (n = 6), we did not inlude this as an outome. Statistial methods Baseline desriptive harateristis were ompared between women with and without M genitalium using x 2 tests of proportions. The ross-setional assoiation between M genitalium and endometritis at baseline was additionally determined using a logisti model, fit with M genitalium, age, rae, N gonorrhoeae and C trahomatis as explanatory variables. Relative risks were alulated for the prospetively determined outomes. Inident endometritis was defined by a negative histologial test for endometritis at baseline followed by a positive histologial ategorisation for endometritis 30 days following treatment. To examine treatment failure, we ategorised persistent endometritis as histologial endometritis identified at both the baseline and 30 day examinations. Logbinomial regressions determined the relative risks and 95% onfidene intervals (CIs) for endometritis at 30 days, inident endometritis, persistent endometritis, reurrent PID, infertility, hroni pelvi pain, pregnany and live birth, and inluded M genitalium, age and rae as explanatory variables. Infertility, pregnany and live birth models were additionally adjusted for self reported infertility at baseline, and models prediting treatment failure were additionally adjusted for interourse between baseline and 30 days and self reported partner treatment. Analyses were onduted first using both ervial and endometrial M genitalium PCR results ombined and were then repeated using only endometrial PCR. All analyses were onduted in the entire ohort and in a subset of women with negative tests for N gonorrhoeae or C trahomatis. SAS version 9.1 for Windows was used for all statistial omparisons. RESULTS We deteted M genitalium in 88 (15%) of women at baseline. Altogether, 11% of ervial speimens and 8% of endometrial speimens were positive for M genitalium; infetions at these sites were highly orrelated (Phi orrelation 0.63, p,0.0001), with 74% of endometrial positive ases also positive at the ervix and 60% of ervial positive ases also positive in the endometrium. Women who tested positive ompared to those who tested negative for M genitalium were more than twie as likely to have histologially onfirmed endometritis at baseline (odds ratio (OR) 2.6, 95% CI 1.5 to 4.6; table 1). After adjustment for age, rae, N gonorrhoeae and C trahomatis, women testing positive for M genitalium were two times more likely to have baseline endometritis (OR 2.0, 95% CI 1.0 to 4.2). Partiipants who tested positive and negative for M genitalium had similar sores for self rated pelvi pain at baseline. However, whereas women who tested positive for M genitalium alone sored their pelvi pain similarly to those who tested positive for C trahomatis alone (p = 0.5), women testing positive for M genitalium alone had self rated pelvi pain sores, whih were signifiantly lower than those among women testing positive for N gonorrhoeae alone at baseline (58.0 (SD 21.9) vs 72.3 (SD 23.9), p = 0.01). Women with versus those without M genitalium identified in endometrial and/or ervial speimens were more likely to be less than 25 years of age, have onurrent N gonorrhoeae and C trahomatis, and report vaginal douhing, drug use and igarette smoking (table 1). Overall, 23 out of 56 women (41%) with M genitalium identified in either the ervix and/or endometrium at baseline had M genitalium persistently identified 30 days following treatment. Of women with endometrial speimens obtained at both baseline and 30 days, 44% (14/32) had persistent endometrial M genitalium deteted. Women with M genitalium identified in the endometrium were 4.5 times more likely to experiene short-term treatment failure, defined by histologial identifiation of endometritis and persistent pelvi pain at the 30 day follow up lini visit (adjusted rate ratio (RR) 4.6, 95% CI 1.1 to 20.1; table 2). Having M genitalium identified in the endometrium at baseline was assoiated with both an inreased risk of inident endometritis at 30 days (adjusted RR 5.0, Sex Transm Infet 2008;84: doi: /sti

3 Table 1 Charateristis of women with and without Myoplasma genitalium identified in the endometrium and/or ervix Charateristi Mg+ n = 88, n (%) Mg2 n = 498, n (%) p Value Histologial endometritis* 43/63 (68.3) 197/439 (44.9) Pelvi pain sore{ (mean SD) 67.7 (SD 21.3) 65.6 (SD 21.5) Co-infetion N gonorrhoeae and/or 43/65 (66.2) 172/435 (39.5), C trahomatis N gonorrhoeae alone 26/59 (44.1) 111/423 (26.2) C trahomatis alone 23/74 (31.1) 91/484 (18.8) M hominis 4/37 (10.8) 17/203 (8.4) U urealytium 1/37 (2.7) 15/203 (7.4) BV 51/80 (63.8) 254/453 (56.1) Demographi Age, 25 years 71/88 (80.7) 319/498 (64.1) > 25 years 17/88 (19.3) 179/498 (35.9) Rae/ethniity Afrian Amerian 69/88 (78.4) 358/498 (71.9) White/Hispani/Other 19/88 (21.6) 140/498 (28.1) Marital status Unmarried 71/78 (91.0) 411/466 (88.2) Married 7/78 (9.0) 55/466 (11.8) Eduation, High shool 38/88 (43.2) 189/497 (38.0) > High shool 50/88 (56.8) 308/497 (62.0) Sexual history History of STD{ 51/86 (59.3) 288/485 (59.4) History of BV 13/86 (15.1) 117/482 (24.3) Sexually ative 78/88 (88.6) 415/498 (83.3) Rare/oasional ondom 60/78 (76.9) 289/415 (69.6) use1 Consistent ondom use" 7/78 (9.0) 57/415 (13.7) > 2 sexual partners 10/88 (11.4) 46/498 (9.2) Behavioural Vaginal douhe, 2+ times 26/88 (29.6) 88/498 (17.7) in past month Drug use 32/88 (36.4) 125/495 (25.3) Current smoker 49/88 (55.7) 194/495 (39.2) *>5 surfae epithelium neutrophils per 6400 field absent of menstrual endometrium and/or >2 stromal plasma ells per 6120 field; {mean omposite pain sore = (mean of urrent pelvi pain sore, average pelvi pain sore and worst pelvi pain sore) 6 10; {history of Neisseria gonorrhoeae, Chlamydia trahomatis or Trihonomas vaginalis; 1ondoms used 0 to 5 out of 10 sexual enounters; "ondoms used in 10 out of 10 sexual enounters. BV, baterial vaginosis; STD, sexually transmitted disease. 95% CI 1.2 to 20.6) and persistent endometritis, identified histologially at both baseline and 30 days following treatment (adjusted RR 4.1, 95% CI 1.4 to 11.9). In models additionally adjusted for N gonorrhoeae and C trahomatis, endometrial M genitalium was assoiated with inident endometritis (adjusted RR 6.0, 95% CI 1.4 to 27.1) and treatment failure (adjusted RR 5.2, 95% CI 0.9 to 30.6), although the assoiation with treatment failure was of borderline statistial signifiane. Results were similar among a subset of women testing negative for C trahomatis and N gonorrhoeae, although ell sizes were small and onfidene intervals large. In this group of women without N gonorrhoeae or C trahomatis, those with M genitalium identified in the endometrium at baseline were nearly nine times as likely to be ategorised as having endometritis at the 30 day examination (adjusted RR 8.8, 95% CI 2.0 to 39.6) and over 13 times as likely to be defined as having inident endometritis at 30 days (adjusted RR 13.4, 2.4 to 75.2). As o-infetion was ommon in this study, models with mirobiologial interation terms were additionally examined. M genitalium did not signifiantly interat with N gonorrhoeae or C trahomatis to additionally influene the risk of inident endometritis or treatment failure. In models adjusting for M hominis and U urealytium, M genitalium was assoiated with almost a 2.5- fold inreased risk of persistent endometritis (RR 2.4, 95% CI 0.5 to 12.4). However, as M hominis and U urealytium were only ultured on a subset of women in the parent PEACH study, a smaller sample size resulted in a wide onfidene interval. Rates of infertility (22%), reurrent PID (31%) and hroni pelvi pain (42%) were high among women testing positive for endometrial M genitalium at baseline. Although the rates of reprodutive morbidity were not signifiantly higher among women testing positive for M genitalium, all relationships were in the hypothesised diretion (table 3). Women with versus those without endometrial M genitalium experiened modest, non-signifiantly elevated risks of reurrent PID, infertility and hroni pelvi pain, and were slightly but non-signifiantly less likely to experiene a pregnany or live birth. DISCUSSION We deteted M genitalium at a high prevalene (15%) among an urban US population of women with non-gonooal, nonhlamydial PID, similar to that found in prior PID studies among Kenyan (16%) 16 and UK women (13%). 15 In the PEACH study, about 14% of women were infeted with C trahomatis, 15% were infeted with N gonorrhoeae and 5% were o-infeted with these two pathogens. 7 Thus, M genitalium was as prevalent as C trahomatis or N gonorrhoeae among this population of women with PID. Women with endometrial M genitalium were over three times more likely to have histologially onfirmed endometritis ompared to women without M genitalium identified at this site. Our study suggests that the relationship between M genitalium and endometritis is independent and ausal, sine among women without onurrent N gonorrhoeae and/or C trahomatis, endometrial M genitalium was assoiated with over a 13-fold risk of inident endometritis at the 30 day follow up visit. Our results are onsistent with previous ross-setional studies assoiating M genitalium with PID Further, we found that although pelvi pain was similar between women testing positive and negative for M genitalium, women who tested positive for M genitalium alone reported signifiantly less pelvi pain than women who tested positive for N gonorrhoeae alone. Pelvi pain sores were lower and similar among women who tested positive for M genitalium alone and C trahomatis alone, suggesting that, like C trahomatis, M genitalium may also play a role in asymptomati or silent PID. To our knowledge, ours is the first study to investigate treatment failure among PID patients with M genitalium identified in the endometrium. Persistene of M genitalium following treatment with a standard Centers for Disease Control and Prevention reommended PID treatment regimen was very high: 44% of women with baseline endometrial positive speimens tested positive again 30 days following treatment. In ontrast, only 2 4% of women in the PEACH study had persistent or reurrent gonooal or hlamydial erviitis when retested at 30 days. 7 Women with M genitalium identified in the endometrium at baseline were four times as likely to experiene persistent endometritis and approximately 4.5 times as likely to experiene treatment failure defined as the presene of both endometritis and pelvi pain 30 days following treatment for PID. 340 Sex Transm Infet 2008;84: doi: /sti

4 Table 2 Endometritis 30 days following treatment with efoxitin and doxyyline and short-term treatment failure (endometritis at 30 days and persistent pelvi pain) among women with and without baseline Myoplasma genitalium (MG) genital trat infetion Outome endometrial Mg+ n (%) n = 88 endometrial Mg2 n (%) n = 498 Several attributes of M genitalium indiate that it is resistant to efoxitin and doxyyline. First, myoplasmal bateria lak a ell wall and are thus resistant to ell wall inhibiting antibiotis. Seond, an M genitalium strain with inreased tetrayline resistane has been isolated 21 and M genitalium is assoiated with persistent non-gonooal urethritis among men treated with tetraylines. 22 Most women with PID are treated with antibiotis direted toward N gonorrhoeae and/or Ctrahomatis, despite the fat that these pathogens aount for only a third to a half of PID ases. Indeed, in the PEACH study approximately 60% of women had non-gonooal, non-hlamydial PID. 7 Over a third of the women had persistent endometritis post treatment, 7 identifying a sizeable portion as having ongoing upper genital trat inflammation and demonstrating that antibiotis used to treat this ritially important upper trat syndrome are suboptimal. M genitalium has demonstrated variable resistane to fluoroquinolones 23 and suseptibility to marolides, although azithromyin resistant strains have reently been identified. 24 A newer quinolone, moxifloxain, has reently been shown to exhibit a high degree of ativity against M genitalium. 21 Randomised linial trials assessing these alternative regimens for the treatment of M genitalium and PID are needed. It is possible that other organisms resistant to doxyyline or efoxitin may have onfounded the relationship between M genitalium and persistent endometritis. However, M genitalium was not assoiated with endometrial M hominis or U urealytium organisms that express tetrayline resistane 25 and ontain tetm genes that enode tetrayline resistane. 26 Further, adjustment for these pathogens only slightly attenuated the relationship between M genitalium and persistent endometritis. Additionally, we reognise that PID may reur among women who engage in risky sexual behaviour during treatment, and this may also onfound treatment failure omparisons. However, in models adjusted for self reported partner treatment and interourse, M genitalium was signifiantly preditive of treatment failure, supporting the idea that M genitalium antibioti resistene may lead to persistent PID. Adjusted RR" Endometrial Mg+ n (%) n = 50 Endometrial Mg2 n (%) n = 561 Adjusted RR" Treatment failure* 8 (40.0) 26 (17.5) 2.6 (0.8 to 8.9) 6 (50.0) 30 (18.5) 4.6 (1.1 to 20.1) Endometritis at 30 days{ 25 (56.8) 119 (39.0) 1.9 (0.9 to 3.9) 19 (70.4) 131 (39.2) 4.0 (1.5 to 10.9) Inident endometritis{ 6 (24.0) 35 (15.8) 1.5 (0.4 to 5.0) 5 (38.5) 37 (15.4) 5.0 (1.2 to 20.6) Persistent endometritis1 17 (47.2) 73 (28.2) 2.1 (1.0 to 4.6) 13 (61.9) 82 (28.8) 4.1 (1.4 to 11.9) *Treatment failure is defined as both endometritis and pelvi pain present at the 30 day lini visit; {All women ategorised as having endometritis at the 30 day lini visit; {inludes women without endometritis at baseline who are ategorised as having endometritis at the 30 day lini visit; 1inludes women who are ategorised as having endometritis at both baseline and 30 days; "Adjusted for age and rae, self reported partner treatment and interourse between baseline and the 30 day lini visit. Table 3 Outome Although a positive M genitalium test was not signifiantly preditive of reprodutive morbidity in our study, results were in the hypothesised diretion. Infertility, hroni pelvi pain and reurrent PID were more ommon among women testing positive for endometrial M genitalium, and women who tested positive were less likely to beome pregnant or have a live birth. Certainly, these reprodutive outomes are more subjet to mislassifiation and bias than shorter term outomes due to loss of follow up and reliane on self reported data. Suh mislassifiation may have biased our results towards the null. Additionally, it is possible that women may have had prior M genitalium infetion that resulted in tubal damage preeding the baseline PEACH study PID episode. As suh prior infetion would not be identified using PCR, whih identifies aute infetion, this may have biased our results towards the null. Indeed, in a study of 308 women undergoing in vitro fertilisation treatment, women determined to have tubal fator infertility were over three times as likely to be seropositive for M genitalium. 27 Moreover, among a study of 212 ouples attending infertility linis, although M genitalium was not deteted by PCR in any ervial swab speimens, M genitalium seropositivity was strongly assoiated with tubal fator infertility. 28 This supports the idea that previous M genitalium infetion may result in permanent damage and olusion of fallopian tubes. Lastly, although we found M genitalium to be assoiated with treatment failure, we have previously reported that short-term markers, inluding pelvi tenderness at 5 and 30 days, are not preditive of reprodutive morbidity in the PEACH study population. 29 As over two-thirds of women in the PEACH study presented for treatment with 3 or more days of pelvi pain, 7 and sine delayed are for PID is assoiated with almost a threefold inreased risk for infertility, 30 all women in the PEACH study may have been at inreased risk for reprodutive sequelae regardless of short-term treatment response. Indeed, women in the PEACH study experiened distressingly high rates of morbidity regardless of mirobial aetiology of PID (infertility 17%, 7 reurrent PID 14% 7 and hroni pelvi pain 37% 31 ). Sequelae and long-term treatment failure among women with and without baseline Myoplasma gentalium (MG) genital trat infetion endometrial Mg+ n (%) n=88 endometrial Mg2 n (%) n = 498 Adjusted RR* Endometrial Mg+ n (%) n=50 Endometrial Mg2 n (%) n = 561 Adjusted RR* Reurrent pelvi 24 (28.2) 98 (20.8) 1.6 (0.8 to 3.1) 15 (30.6) 111 (20.8) 1.8 (0.8, 3.8) inflammatory disease Infertility 15 (17.4) 95 (19.4) 1.4 (0.6 to 2.9) 11 (22.0) 104 (18.9) 1.1 (0.7 to 4.0) Chroni pelvi pain 37 (43.5) 198 (41.4) 1.6 (0.9 to 2.9) 21 (42.0) 226 (42.1) 1.3 (0.6 to 2.7) Pregnany 53 (61.6) 278 (56.9) 0.8 (0.4 to 1.5) 29 (58.0) 317 (57.6) 0.7 (0.3 to 1.4) Live birth 34 (50.7) 207 (48.5) 0.7 (0.3 to 1.3) 19 (46.3) 236 (49.3) 0.6 (0.3 to 1.3) *All models are adjusted for age, rae, Neisseria gonorrhoeae and Chlamydia trahomatis. Infertility, pregnany and live birth models are additionally adjusted for self reported infertility at baseline. Sex Transm Infet 2008;84: doi: /sti

5 Key messages Myoplasma genitalium is frequently deteted from the ervix and endometrium of women with linially suspeted pelvi inflammatory disease (PID). M genitalium is assoiated with endometritis and short-term PID treatment failure, as evidened by persistent endometritis and ontinued pelvi pain. Cefoxitin and doxyyline, a Center for Disease Control reommended PID treatment regimen, is ineffetive for the treatment of M genitalium upper genital trat infetion. Certainly, women with M genitalium identified in either the ervix or endometrium had high rates of infertility (18%), reurrent PID (28%) and hroni pelvi pain (44%). These infertility rates are approximately 2.5 times higher than that reported from a study utilising 2002 National Survey of Family Growth data, 32 suggesting that preservation of fertility may be suboptimal for many women treated for PID. Reommended PID treatment regimens are based on linial trial data demonstrating overall high rates of linial ure. PID is well reognised though as having a polymirobial aetiology, and not all mirobial infetions may respond equally well to the same antimirobial. In our study of women with linially suspeted PID, we found M genitalium to be assoiated with endometritis and short-term PID treatment failure, as evidened by persistent endometritis and ontinued pelvi pain. We onlude that efoxitin and doxyyline, a Center for Disease Control reommended PID treatment regimen, is ineffetive for the treatment of M genitalium upper genital trat infetion. Aknowledgements: Investigators involved in the PEACH Study inlude A Amortegui; S L Hendrix; S L Hillier; R L Holley; D B Nelson; J Nihols Jr; J Peipert; H Randall; D Shubek; S J Sondheimer; D E Soper; R L Sweet; W Trout; G Truo; H C Wiesenfeld and T Yalinkaya. We thank and aknowledge the efforts of interviewers who reruited and interviewed study partiipants: S Allen, A Baum, C Beker, H Cohen-Webb, A Cooper, P Crowner, L Curll, J Faas, A Farmer, E Hoffman, A Holdredge, A Howell, S Kay, F Leboeuf, IMaio, K Martin, M MNamee, A Meers, K Miller, A Montagno, J Mowery, J Mitton, C Myers, B Nobels, T Pealer, A Rideout, G Rothstein, C Sams, T Shuda, B Shiavoni, M Sott, K Timbers, S Whitaker, L Williams and M Vineti. We also gratefully aknowledge onsultants T Songer, J Lave and S Kelsey, and tehnial assistant D Bass. Funding: HS from the Ageny for Healthare Researh and Quality Development and 1 R01 AI A2 from the National Institute of Allergy and Infetious Diseases. Competing interests: None. 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